Elevated intraocular pressure (IOP) has long been assumed to play a causative role in glaucomatous damage to the optic nerve head (ONH). There is compelling evidence to suggest that the elderly and individuals of African descent are at much greater risk for the onset and progression of glaucomatous damage at elevated levels of IOP. In this proposal, we test the hypothesis that age- and race-related differences in ONH biomechanics may contribute to this difference in risk. Using high-resolution, fluorescent, three-dimensional (3D) reconstructions of the ONH, and principles of biomechanical engineering, we will study the mechanical effects of elevated IOP in glaucoma. However, the relationship between advancing age, African ancestry, and the mechanical effects of elevated IOP is still unclear. How do age- and race-related differences in ONH structure and biomechanics increase its susceptibility to IOP? Is the robustness of the ONH connective tissues the key to understanding individual susceptibility to glaucoma? What role does the structural stiffness of the lamina cribrosa and peripapillary sclera play in the increased risk for glaucomatous progression in the elderly and in individuals of African descent? To answer these questions, we will use novel methods to elucidate the relationship between age, race, and the IOP-induced deformation of ONH connective tissues. By ONH biomechanics we mean the interactions between IOP and connective tissue structural stiffness (the combination of tissue architecture and material properties) in the ONH and peripapillary sclera. The immediate goals of this project are to characterize age- and race-related differences in ONH biomechanics and elucidate their effects on ONH susceptibility. Our long-term goal is to develop clinical diagnostics and interventions designed to manage each important biomechanical risk factor in the development and progression of glaucoma. To accomplish our immediate goals, we will build digital three-dimensional reconstructions of human ONH tissues from donors of African and European descent, quantify the ONH connective tissue architecture within each reconstruction, and build computational finite element models of the ONH connective tissues to estimate their biomechanical response to normal and elevated levels of IOP.